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工程化光热诊疗纳米级金属有机框架用于多模态成像引导的癌症治疗。

Engineering Phototheranostic Nanoscale Metal-Organic Frameworks for Multimodal Imaging-Guided Cancer Therapy.

机构信息

Institute of Medical Engineering, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center , Xi'an, Shaanxi 710061, China.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University , Xiamen, Fujian 361102, China.

出版信息

ACS Appl Mater Interfaces. 2017 Jan 25;9(3):2040-2051. doi: 10.1021/acsami.6b11579. Epub 2017 Jan 11.

Abstract

Many photoresponsive dyes have been utilized as imaging and photodynamic/photothermal therapy agents. Indocyanine green (ICG) is the only near-infrared region (NIR) organic dye for clinical applications approved by the United States Food and Drug Administration; however, the clinical application of ICG is limited by its poor aqueous solubility, low cancer specificity, and low sensitivity in cancer theranostics. To overcome these issues, a multifunctional nanoplatform based on hyaluronic acid (HA) and ICG-engineered metal-organic framework MIL-100(Fe) nanoparticles (MOF@HA@ICG NPs) was successfully developed for imaging-guided, anticancer photothermal therapy (PTT). The synthesized NPs showed a high loading content of ICG (40%), strong NIR absorbance, and photostability. The in vitro and in vivo imaging showed that the MOF@HA@ICG NPs exhibited greater cellular uptake in CD44-positive MCF-7 cells and enhanced tumor accumulation in xenograft tumors due to their targeting capability, compared to MOF@ICG NPs (non-HA-targeted) and free ICG. The in vitro photothermal toxicity and in vivo PTT treatments demonstrated that MOF@HA@ICG NPs could effectively inhibit the growth of MCF-7 cells/xenograft tumors. These results suggest that MOF@HA@ICG NPs could be served as a new promising theranostic nanoplatform for improved anticancer PTT through cancer-specific and image-guided drug delivery.

摘要

许多光响应染料已被用作成像和光动力/光热治疗剂。吲哚菁绿(ICG)是唯一一种获得美国食品和药物管理局批准的临床应用近红外(NIR)有机染料;然而,ICG 的临床应用受到其较差的水溶性、低癌症特异性和低癌症治疗敏感性的限制。为了克服这些问题,成功开发了一种基于透明质酸(HA)和 ICG 工程化的金属有机骨架 MIL-100(Fe)纳米粒子(MOF@HA@ICG NPs)的多功能纳米平台,用于成像引导、抗癌光热治疗(PTT)。合成的 NPs 具有较高的 ICG 负载含量(40%)、强近红外吸收和光稳定性。体外和体内成像研究表明,与 MOF@ICG NPs(非 HA 靶向)和游离 ICG 相比,MOF@HA@ICG NPs 由于其靶向能力,在 CD44 阳性 MCF-7 细胞中具有更高的细胞摄取率,并在异种移植瘤中增强了肿瘤积累。体外光热毒性和体内 PTT 治疗表明,MOF@HA@ICG NPs 能够有效抑制 MCF-7 细胞/异种移植瘤的生长。这些结果表明,MOF@HA@ICG NPs 可作为一种新的有前途的治疗纳米平台,通过癌症特异性和图像引导的药物递送来改善抗癌 PTT。

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